Comparative Morphological and Molecular Genetic Characteristics of Cell and Tissue Strains of Experimental Rat Glioma 10-17-2 (Astrid-17).

In order to obtain models of gliomas of varying degrees of malignancy, we performed morphological and molecular genetic study of a tissue strain of glioma 10-17-2 (Astrid-17) obtained by intracranial passaging of tumor fragments of chemically induced rat brain tumor, and a cell strain isolated from it. More or less pronounced changes in the expression levels of Mki67, Trp53, Vegfa, and Gfap genes in the tissue and cell strain of glioma 10-17-2 (Astrid-17) compared with intact brain tissue were shown. The tissue model of glioma 10-17-2 (Astrid-17) according to the studied characteristics shows features of grade 3-4 astrocytoma and the cellular model - grade 2-3 astrocytoma.

Characteristics of the Antitumor Effect of Doxorubicin and Pegylated Hyaluronidase on Models of Rat Brain Tumors.

Hyaluronidase increases tissue permeability and diffusion of the extracellular fluid by cleaving hyaluronan, the primary component of the extracellular matrix. Hyaluronidase pegylation (Hyal-PEG) decreases its clearance and enhances biodistribution. The pro- and anticancer activity of Hyal-PEG and a combination of Hyal-PEG with doxorubicin were studied in vitro (morphological analysis of rat glioblastoma 101.8 spheroids) and in vivo (by the survival time of rats after intracerebral transplantation of the tumor and morphological analysis). In the presence of doxorubicin and Hyal-PEG in the culture medium in vitro, spheroids lost their ability to adhere to the substrate and disintegrate into individual cells. Intracerebral transplantation of the tumor tissue with Hyal-PEG did not accelerate glioblastoma growth. The mean survival time for animals receiving transplantation of the tumor alone and in combination with Hyal-PEG was 13 and 20 days, respectively. In one rat with transplanted tumor and Hyal-PEG, this parameter increased by 53%. The survival time of rats receiving systemic therapy with doxorubicin and Hyal-PEG significantly increased (p=0.003). Antitumor effect of therapeutic doses of doxorubicin combined with Hyal-PEG was demonstrated on the model of rat glioblastoma 101.8 in vitro. Hyal-PEG inhibited adhesion of tumor cells, but did not cause their death. Transplantation of Hyal-PEG-treated tumor did not reduce animal survival time. Systemic administration of therapeutic doses of doxorubicin with Hyal-PEG increased survival time of rats with glioblastoma 101.8.

The Effect of Therapy Regimen on Antitumor Efficacy of the Nanosomal Doxorubicin against Rat Glioblastoma 101.8.

One of the key problems of glioblastoma treatment is the low effectiveness of chemotherapeutic drugs. Incorporation of doxorubicin into PLGA nanoparticles allows increasing the antitumor effect of the cytostatics against experimental rat glioblastoma 101.8. Animal survival, tumor volume, and oncogene expression in tumor cells were compared after early (days 2, 5, and 8 after tumor implantation) and late (days 8, 11, and 14) start of the therapy. At late start, a significant increase in the expression of oncogenes Gdnf, Pdgfra, and Melk and genes determining the development of multidrug resistance Abcb1b and Mgmt was revealed. At early start of therapy, only the expression of oncogenes Gdnf, Pdgfra, and Melk was enhanced. Early start of treatment prolonged the survival time and increased tumor growth inhibition by 141.4 and 95.7%, respectively, in comparison with the untreated group; these differences were not observed in the group with late start of therapy. The results indicate that the time of initiation of therapy is a critical parameter affecting the antitumor efficacy of DOX-PLGA.

Morphofunctional Characteristics of Lung Macrophages in Rats with Acute Respiratory Distress Syndrome.

A comprehensive morphofunctional study of the lungs and alveolar macrophages was carried out in Sprague-Dawley rats with acute respiratory distress syndrome (n=10) induced by intratracheal administration of E. coli LPS 0111:B4 in a dose of 15 mg/kg. On the first day after LPS administration, bronchopneumonia was observed in the lungs, the number of macrophages of the bone marrow origin and the number of M1 macrophages with the proinflammatory phenotype in the bronchoalveolar lavage increased, the expression of proinflammatory cytokines increased and the expression of anti-inflammatory cytokines decreased, which was accompanied by an increase in LPS and C-reactive protein in the blood serum. The revealed changes correspond to the development of acute respiratory distress syndrome in humans, and the decrease in the number of macrophages in the lungs and their predominant polarization to the M1-proinflammatory phenotype substantiate the use of cell therapy with reprogrammed M2 macrophages.

[Bacterial mixed infection in women with chronic recurrent cystitis].

AIM: To study microbial repertoire of urine in healthy women and patients with chronic recurrent cystitis (CRC) including facultative anaerobic (FA) and non-clostridial anaerobic (NCA) bacteria. MATERIALS AND METHODS. Triple bacteriological study of urine was performed in three groups of women: group I--22 healthy virgin women aged 18- 25 years, group II--24 women aged 18 - 25 years with regular sexual contacts, group III--72 women aged 20 - 60 years with CRC, before antibacterial therapy. Bacteriological method was used to study qualitative and quantitative composition of urine microflora. RESULTS: In all subjects from groups I and II aerobic-anaerobic associations with predomination of coagulase-negative staphylococci (CNS), corynebacteria, peptococci, and peptostreptococci were isolated from urine. Quantity of isolated NCA bacteria was significantly higher than that of FA. In etiologic structure of CRC, NCA bacteria, enterobacteria, and CNS predominated. Spectrum of NCA bacteria isolated from patients with CRC was wider and level of bacteriuria--higher (p < 0.05) compared to groups I and II. Bacteria were identified in aerobic-anaerobic associations. In 85.7% of cases following NCA were identified in biopsy samples: Propionibacterium sp. (41.8%), Peptococcus sp. (35.7%), Eubacterium sp. (28.6%), Peptostreptococcus sp. (14.3%), and Bacteroides sp. (14.3%). Aerobic-anaerobic associations were observed in 7.1% of samples. CONCLUSION: Urine of healthy women is not sterile. Aerobic-anaerobic mixed infections were detected in patients with CRC that should take into account during diagnostics and treatment of this disease.

[Etiological structure and antibiotic sensitivity of uropathogens in chronic recurrent infection of the lower urinary tract].

While acute infections of the lower urinary tract (UT) have been studied in detail and antibiotic therapy of such infections is well known, etiology and choice of antibacterial treatment in recurrent chronic UT infection are not so clear. In our trial we aimed at elucidation of etiological structure of chronic cystitis recurrences by means of microbiological investigation of urine samples from 72 women on extended spectrum of nutrient media. In all the cases urine was infected with both aerobic and non-clostridial anaerobic bacteria. We determined prevalent pathogens and their antibiotic sensitivity and compared them with standard pathogens and their sensitivity in acute lower UT infection. We came to the conclusion that it is necessary to develop new recommendations on antibiotic treatment of recurrent chronic cystitis in women.